Aspergillus fumigatus pan-genome analysis identifies genetic variants associated with human infection

被引:66
作者
Barber, Amelia E. [1 ,9 ]
Sae-Ong, Tongta [2 ]
Kang, Kang [2 ]
Seelbinder, Bastian [2 ]
Li, Jun [3 ,4 ]
Walther, Grit [5 ]
Panagiotou, Gianni [2 ,6 ,7 ]
Kurzai, Oliver [1 ,5 ,8 ]
机构
[1] Hans Knoell Inst, Res Grp Fungal Sept, Leibniz Inst Nat Prod Res & Infect Biol, Jena, Germany
[2] Hans Knoell Inst, Res Grp Syst Biol & Bioinformat, Leibniz Inst Nat Prod Res & Infect Biol, Jena, Germany
[3] City Univ Hong Kong, Dept Infect Dis & Publ Hlth, Jockey Club Coll Vet Med & Life Sci, Hong Kong, Peoples R China
[4] City Univ Hong Kong, Sch Data Sci, Hong Kong, Peoples R China
[5] Hans Knoell Inst, Natl Reference Ctr Invas Fungal Infect NRZMyk, Leibniz Inst Nat Prod Res & Infect Biol, Jena, Germany
[6] Univ Hong Kong, Dept Med, Hong Kong, Peoples R China
[7] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Peoples R China
[8] Univ Wurzburg, Inst Hyg & Microbiol, Wurzburg, Germany
[9] Hans Knoell Inst, Jr Res Grp Fungal Informat, Leibniz Inst Nat Prod Res & Infect Biol, Jena, Germany
关键词
PHYLOGENETIC ANALYSIS; IN-VITRO; VIRULENCE; ALIGNMENTS; SEQUENCE;
D O I
10.1038/s41564-021-00993-x
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Aspergillus fumigatus is an environmental saprobe and opportunistic human fungal pathogen. Despite an estimated annual occurrence of more than 300,000 cases of invasive disease worldwide, a comprehensive survey of the genomic diversity present in A. fumigatus-including the relationship between clinical and environmental isolates and how this genetic diversity contributes to virulence and antifungal drug resistance-has been lacking. In this study we define the pan-genome of A. fumigatus using a collection of 300 globally sampled genomes (83 clinical and 217 environmental isolates). We found that 7,563 of the 10,907 unique orthogroups (69%) are core and present in all isolates and the remaining 3,344 show presence/absence of variation, representing 16-22% of the genome of each isolate. Using this large genomic dataset of environmental and clinical samples, we found an enrichment for clinical isolates in a genetic cluster whose genomes also contain more accessory genes, including genes coding for transmembrane transporters and proteins with iron-binding activity, and genes involved in both carbohydrate and amino-acid metabolism. Finally, we leverage the power of genome-wide association studies to identify genomic variation associated with clinical isolates and triazole resistance as well as characterize genetic variation in known virulence factors. This characterization of the genomic diversity of A. fumigatus allows us to move away from a single reference genome that does not necessarily represent the species as a whole and better understand its pathogenic versatility, ultimately leading to better management of these infections. The de novo genome assembly and analysis of 300 Aspergillus fumigatus genomes from environmental and clinical isolates provides insight into the pan-genome of this important human fungal pathogen. Genome-wide association studies identify genomic variation associated with human infection and triazole resistance, and reveal potential therapeutic antifungal targets.
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收藏
页码:1526 / +
页数:18
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